We have previously reported the presence of the Interleukin-4 receptor (IL-4R) on methylcholanthrene (MCA-106, MCA-102 and MC-38) and viral DNA (G-2TS and 14-2TS) induced murine sarcoma cells. These receptors are similar in characteristics to that observed by us on TIL cells and by others on T and B lymphocytes, mast cells and macrophages. These receptors are internalized after binding to a chimeric protein between IL-4 and pseudomonas exotoxin (IL-4-PE40). Using IL-4PE40, we observed that IL-4-PE40 was cytotoxic (determined by inhibition of protein synthesis by [(3)H]-Leucine uptake) to MCA-106 tumor cells in a dose dependent manner. IL-4-PE40 asp(553), a chimeric mutant protein which can bind to IL-4 receptors but does not have the capability to inhibit protein synthesis was not cytotoxic to tumor cells. These studies suggest that IL-4R on murine MCA-106 sarcoma cells is internalized when occupied by IL-4-PE40 and may be functional. taken together, these data suggest that IL-4 receptor may be a target for IL-4-toxin therapy. Now we have found that TNF-alpha upregulates IL-4 receptors on tumor cells. We are actively pursuing our research to investigate the mechanism and possible role of augmented expression of IL-4 receptors on tumor cells.